Neurosciences- Lecture 2 Virus associated meningitis Polio Virus

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1 Al- Balqa Applied University Faculty of Medicine Neurosciences- Lecture 2 Virus associated meningitis Polio Virus Dr. Hala Al Daghistani The most important Enteroviruses are the three poliovirus serotypes (types 1, 2, and 3). Improvement of sanitary conditions tends to impede spread of the viruses They are inactivated when heated at 55 C for 30 minutes, but Mg2+ prevents this inactivation. Virus is present in sewage and can serve as a source of contamination of water used for drinking, bathing, or irrigation. There is a direct correlation between poor hygiene, sanitation, and crowding and the acquisition of infection and antibodies at an early age. PATHOGENESIS The mouth is the portal of entry of the virus, and primary multiplication takes place in the oropharynx or intestine. The virus is regularly present in the throat and in the stools before the onset of illness. Poliovirus can spread along axons of peripheral nerves to the CNS, where it continues to progress along the fibers of the lower motor neurons to increasingly involve the spinal cord or the brain. Poliovirus invades certain types of nerve cells, and in the process of its intracellular multiplication, it may damage or completely destroy these cells. The changes that occur in peripheral nerves and voluntary muscles are secondary to the destruction of nerve cells. In addition to pathologic changes in the nervous system, there may be myocarditis, lymphatic hyperplasia, and ulceration of Peyer patches.

2 Clinical Manifestations Most infections (perhaps 90%) are either completely subclinical or so mild that they do not come to attention. When disease does result, the incubation period ranges usually between 7 and 14 days. Three types of disease can be observed. 1. Abortive poliomyelitis is a nonspecific febrile illness of 2- to 3-day duration with no signs of CNS localization. The patient has only a minor illness, characterized by fever, malaise, drowsiness headache, nausea, vomiting, constipation, and sore throat in various combinations. Recovery occurs in a few days. 2. Nonparalytic poliomyelitis (aseptic meningitis)is characterized by signs of meningeal irritation (stiff neck, pain, and stiffness in the back) in addition to the signs of abortive poliomyelitis; recovery is rapid and complete, usually within a few days (The nerve cells involved are not sufficient in number to result in clinically evident weakness) 3. Paralytic poliomyelitis, occurs in less than 2% of infections. There are signs of meningeal irritation, but the hallmark of paralytic poliomyelitis is asymmetric flaccid paralysis resulting from lower motor neuron damage (Here large numbers of the nerve cells are rendered useless and the muscles which they innervate are unable to cause motion). 4. Progressive Postpoliomyelitis Muscle Atrophy, a recrudescence of paralysis and muscle wasting has been observed in individuals decades after their experience with paralytic poliomyelitis. Although progressive postpoliomyelitis muscle atrophy is rare, it is a specific syndrome. It does not appear to be a consequence of persistent infection but rather a result of physiologic and aging changes in paralytic patients already burdened by loss of neuromuscular functions. Laboratory Diagnosis The virus may be recovered from throat swabs taken soon after onset of illness and from rectal swabs or stool samples collected over long periods. No permanent carriers have been identified among immunocompetent individuals, but long-term excretion of poliovirus has been observed in some immunodeficient persons. Poliovirus is uncommonly recovered from the cerebrospinal fluid unlike some coxsackieviruses and echoviruses. Cytopathogenic effects appear in 3 6 days.

3 An isolated virus is identified and typed by neutralization with specific antiserum. Virus can also be identified by polymerase chain reaction (PCR) assays. Immunity is permanent to the virus type causing the infection and is predominantly antibody mediated. PREVENTION Two types of poliovirus vaccines are currently licensed (Each contains all three viral serotypes). - Inactivated polio vaccine (SALK) IPV, a vaccine that contains three types of inactivated poliomyelitis viruses and induces immunity against the disease. - live oral attenuated virus vaccine (SABIN). Oral polio vaccine (OPV) is composed of live, attenuated viruses that have undergone serial passage in cell cultures. Produces antibodies to all three serotypes in more than 95% of recipients - As with IPV, recall boosters are recommended to maintain adequate antibody levels. - One disadvantage of OPV is the risk of vaccine-associated paralytic disease in some recipients, including immunocompromised persons. Cryptococcus spp Cryptococcus neoformans Cryptococcus neoformans is a yeast that produces a characteristic capsule, extending the overall diameter. This capsule is unique among pathogenic fungi and is a complex polysaccharide polymer, the major component of which is Glucuronoxylomannan (GXM). Capsule production varies by strains and with environmental conditions. C. neoformans grows at 35 to 37 C on a variety of common media, including blood agar, chocolate agar, and Sabouraud s agar. Mucoid, bacteria-like colonies are produced in 2 to 3 days. In addition to the capsule, extracellular products include a urease enzyme and melanin pigment.

4 Cryptococcosis The primary disease caused by cryptococci is a chronic meningitis. The onset is slow, even insidious, with low-grade fever and headache progressing to altered mental state and seizures. Most patients have some obvious form of immune compromise, although some show no demonstrable immune defect. EPIDEMIOLOGY C. neoformans is found throughout the world, particularly in soil contaminated with pigeon or other bird droppings. The birds themselves are not ill. The cryptococci in the soil produce few or no capsules, which makes them more readily aerosolized. Inhalation of yeast cells from these sites is the presumed mode of transmission. Cryptococcosis occur in immunocompromised patients or in those treated with immunosuppressive agents (eg, steroids). Case-to-case transmission has not been documented.

5 PATHOGENESIS - Following inhalation, the yeast begins to overproduce the polysaccharide capsule, which determines virulence. The capsule is antiphagocytic and has a number of other immunomodulating effects including: 1. binding to complement components while at the same time reducing the ability of polymorphonuclear neutrophils (PMNs) and macrophages to phagocytose and kill cryptococci. This may be due to the combination of the massive size of the capsule and the way in which it binds C3. 2. The capsule can interfere with antigen presentation and the development of T cell mediated immune processes. - Cryptococci are also able to oxidize exogenous catecholamines to produce melanin, a process that may protect them from the oxidative injury of phagocytes. - Production enough capsule can be readily detected in the blood and other body fluids. - Tissue reaction to C. neoformans varies from little or none to purulent or granulomatous. C R Y P T O C O C C O S I S : Clinical aspects Meningitis is the most commonly recognized form of cryptococcal disease; it usually has a slow, insidious onset with relatively nonspecific findings until late in its course. Intermittent headache, irritability, dizziness, and difficulty with complex cerebral functions appear over weeks or months with no consistent pattern. Also, seizures, cranial nerve signs, dementia and decreased levels of consciousness. DIAGNOSIS Typical cerebrospinal fluid (CSF) findings in cryptococcal meningitis are increased pressure, pleocytosis (usually more than 100 cells) with predominance of lymphocytes, and depression of glucose levels. In some cases, one or all of these findings may be absent, yet cryptococci are isolated on culture.

6 Cryptococcal capsules are demonstrable in CSF in roughly 50% of cases by mixing centrifuged sediment with India ink and examining the mixture under the microscope. In the isolation of C. neoformans, the volume of CSF sampled is important. The number of organisms present may be small enough to require a substantial volume of fluid (30 ml) to yield a positive culture. If Cryptococcosis is suspected and cultures are negative, detection of the GXM polysaccharide antigen in the CSF or serum by latex agglutination or enzyme immunoassay methods is recommended. These tests are very sensitive and specific, and their quantitation has prognostic significance. A rising antigen level indicates progression and a declining titer is a favorable sign.